Investigations are being performed in mouse and man to further elucidate the nature of genetic determination of histocompatibility antigens as related to the major histocompatibility complex. Experiments in mice revolve primarily around the obtaining of new recombinants (or testing of those obtained by others) to map the genes responsible for mixed leukocyte culture of graft versus host reactivity. Genes isolated in recombinant mice will also be evaluated for their effect on skin graft survival. In addition in the mouse studies (as well as in the human studies) the interaction between the genes responsible for mixed leukocyte culture activation and those responsible for the determination of the serologically defined histocompatibility antigens will be evaluated using the mixed leukocyte culture and cell mediated lympholysis assays. In man the thrust of investigation will be to define the genes responsible for mixed leukocyte culture activation. This will be done through the use of homozygous "typing cells" obtained from the offspring of first cousin marriages or from individuals who are phenotypically identical for the four HL-A SD antigens. In addition protocols involving "suicide techniques" will be used in this regard.